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Nutritional Epidemiology

Body Mass Index Is an Important Determinant of Methylation Biomarkers in Women of Reproductive Ages^1,2

³ Departments of Obstetrics and Gynecology/Division of Obstetrics and Prenatal Medicine, University Medical Centre, Rotterdam 3015 GE, The Netherlands ⁴ Pediatrics/Division of Pediatric Cardiology, University Medical Centre, Rotterdam 3015 GE, The Netherlands ⁵ Public Health, University Medical Centre, Rotterdam 3015 GE, The Netherlands ⁶ Clinical Chemistry, University Medical Centre, Rotterdam 3015 GE, The Netherlands ⁷ Internal Medicine, University Medical Centre, Rotterdam 3015 GE, The Netherlands ⁸ Epidemiology, University Medical Centre, Rotterdam 3015 GE, The Netherlands ⁹ Clinical Genetics, Erasmus Medical Center, University Medical Centre, Rotterdam 3015 GE, The Netherlands ¹⁰ Division of Human Nutrition, Wageningen University, Wageningen 6703 HD, The Netherlands

B vitamin deficiencies lead to moderate hyperhomocysteinemia, which has been associated with health and disease. However, concomitant derangements in cellular methylation, reflected by altered plasma S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) concentrations, may be the primary cause. Therefore, we identified determinants of homocysteine, SAM, and SAH concentrations in 336 women, aged 20–48 y, as part of a large study focusing on risk factors for reproductive disorders. Blood was obtained to determine plasma SAM, SAH, and total homocysteine (tHcy), serum vitamin B-12 and folate, RBC folate concentrations, and the related single nucleotide polymorphisms 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C > T and 1298A > C, methionine synthase reductase (MTRR) 66A > G, and nicotinamide N-methyltransferase IVS1–151G > A. Questionnaires provided information on demographics, lifestyles, and nutrient intakes. Correlation coefficients were calculated and multivariable associations were assessed with a general linear model. Serum folate was positively correlated with SAM concentrations (r = 0.159; P = 0.004). Folate and vitamin B-12 were not correlated with SAH concentrations or the SAM:SAH ratio but were inversely correlated with tHcy concentrations (serum folate r = –0.324; RBC folate r = –0.294; vitamin B-12 r = –0.307; P < 0.01). From the multivariable analysis, BMI was the strongest determinant of SAM (standardized β = 19.145; P < 0.001) and SAH concentrations (standardized β = 3.241; P = 0.010). MTHFR 677TT (standardized β = 0.195; P = 0.001), B vitamin supplement use (standardized β = –0.156; P < 0.001) and dietary protein intake (standardized β = –0.011; P < 0.001) were the strongest determinants of tHcy concentrations. Thus, the determinants of SAM and SAH differ from those of tHcy concentrations. Given that BMI was a strong determinant of SAM concentrations, it should be included in future studies on cellular methylation.

^* To whom correspondence should be addressed. E-mail: r.steegers{at}erasmusmc.nl.

Manuscript received 13 May 2009. Initial review completed 29 June 2009. Revision accepted 13 September 2009.